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Extracolonic Causes of Constipation

Lifestyle

Dietary Fiber

In clinical practice, it is commonly accepted that fiber therapy and stool-bulking agents are the main therapeutic agents of choice in the initial management of primary constipation. Several clinical trials have been performed on the effects of fiber therapy and constipation. Meta-analyses of these trials have had discordant conclusions. In one study, a total of seven double-blind, placebo-controlled trials were analyzed; five of the studies resulted in improvement in overall symptoms, an increase in fecal weight and frequency, and decreased transit time. However, another meta-analysis reviewed 13 clinical trials, and only four found beneficial results. Moreover, the improvements noted were in several nonspecific outcomes, such as ease of stool passage and frequency of satisfaction with bowel movements, and no significant improvement was noted in the more specific symptoms such as stool frequency, abdominal pain, and bloating. Reviews of fiber therapy have pointed out that the most common reason for failure of fiber treatment is noncompliance. In an ongoing prospective study among female registered nurses in the United States, a total of 3327 out of 62,036 women reported constipation. Intake of dietary fiber based on a self-reported food-frequency questionnaire was correlated with the prevalence of constipation. Multiple logistic regression analysis demonstrated that higher dietary fiber intake was associated with a decreased prevalence of constipation. The study has shown that women who had approximately 20 g daily of fiber had a threefold lower prevalence of constipation compare to women who had about 7g daily of fiber. In light of the conflicting evidence regarding the benefit associated with higher fiber intake and its efficacy in the management of constipation, the current recommendation is that since increasing dietary fiber and hydration is safe and can be prescribed as placebo, it is an important therapeutic modality in the empiric management of constipation.

Dietary_Fiber

Physical Activity

The effect of exercise and physical activity on the gastrointestinal system is an area of emerging interest. A major function of colonic motor activity is the propulsion of colonic contents in the aborad direction; the available literature on the net effects of exercise and physical activity on colonic transit is, at present, controversial. Along with increased ample hydration and high-fiber diet, regular physical exercise has been advocated as the standard, first-line treatment of primary constipation. This recommendation is based on the observation that patients who have decreased mobility are more susceptible to constipation, and from studies suggesting that exercise accelerates gastrointestinal transit, yet there has been no conclusive evidence supporting the use of exercise as therapy for constipation. In one study, information concerning bowel habits was gathered from a representative sample of 14,407 United States adults in the first National Health and Nutrition Examination Survey in 1971 to 1975 and approximately 10 years later among the same individuals. The prevalence of self-reported constipation and infrequent defecation (three or fewer bowel movements per week) increased with aging, and women were more likely than men to report constipation (20.8% vs. 8.0%, p < .05) and infrequent defecation (9.1% vs. 3.2%, p < .05). The study concluded that along with female gender, black race, fewer years of education, and symptoms of depression, low physical activity was one of the independent risk factors for impairment in bowel function.

Bi and Triadafilopolous critically analyzed two studies that reported a significant reduction in transit time after aerobic exercise. In one study that was reviewed, the authors were critical of the methodology, noting that a standardized diet was not given to the cohorts, suggesting that this feature might have affected colonic transit time. The other study that has shown an increase in gastrointestinal transit after aerobic exercise was criticized for lack of dietary control, and the serial nature of 1-week crossover trial among cycling, running, and rest.

Meshkinpour et al studied eight subjects, seven of whom were women with chronic idiopathic constipation, for a 6-week study period that included 2 weeks of rest and 4 weeks of regular exercise. The subjects exercised 1 hour each day, 5 days per week, using a pedometer to objectively assess their overall physical activity. A diary was kept to record the number and consistency of their bowel movements and the amount of straining required for defecation. Results of the study revealed that patients covered 1.9 ± 0.3 and 3.2 ± 0.3 miles/day in the rest period and during the exercise period (p < .007). Despite this level of exercise, the authors noted that the subjects did not improve their constipation indices, which were 9.1 ± 0.7 and 8.6 ± 1.1 in the rest and exercise periods, respectively (p = ns). Thus, the authors concluded that physical activity does not play a role in the management of chronic idiopathic constipation. Using solid-state manometry catheters, Rao et al studied 12 healthy subjects, six of whom were females. These subjects were then instructed to exercise on a stationary cycle ergometer for a period of 15 minutes alternating with 15 minutes of rest. Colonic motor activity, illustrated by number of waves, mean amplitude of waves, and area under the curve, was analyzed before and after the exercise period. The results of the study were contrary to popular belief, as the data have suggested that the incidence of pressure waves and the area under the pressure curve waves were significantly lower during exercise. Moreover, the authors found that with a higher intensity of exercise, there was an associated greater reduction in motor activity.

Physical_Activity

In summary, the benefits of physical activity and exercise may be related to cardiovascular enhancement, and future studies focusing on the effect of physical activity may elucidate the risk of constipation associated with physical inactivity.

Social Habits

Although it may be intuitive that personal and social habits, which include sleeping, bowel hygiene, and lifestyle, are likely to influence an individual’s bowel habits, a literature review found that these factors are not as systematically studied as possible etiologies of constipation. A study on the effect of transatlantic travel on the bowel habits of 77 individuals, 40 of whom were women, hypothesized that with the social changes associated with travel, such as varied diet, different timetables, and problems related to lavatory use, travelers would be more prone to constipation. The participants recorded their regular bowel habits by answering an 11-item questionnaire 1 month before, during, and after the trip. Stool consistency using the Bristol Stool Form Scale, jet lag caused by the trip using the Columbia Jet Lag Scale questionnaire, and colonic transit time using radiopaque markers before and during the trip were the outcome variables of interest. The authors found that there was a difference in bowel movements per day (before the trip, 0.97 ± 0.07 vs. after the trip, 0.68 ± 0.06), where there was a significant decrease after the trip (p < .05). However, comparing the colonic transit time between the two periods did not reveal any significant differences (before the trip, 36.7 ± 4.2 hours vs. after the trip, 36.2 ± 2.8 hours, p = ns). The authors concluded that traveling may induce changes in bowel movements, and that indeed, a significant proportion of the subjects did complain of having constipation. The authors have suggested that the defecatory frequency decrease associated with traveling may be related to jetlag and changes in physical activity and diet, and maybe normal consequences of flying.

Psychological

In clinical practice and studies, it is recognized that there is a strong relationship between gastrointestinal symptoms and psychiatric, mood, and eating disorders. Acknowledging that there may a referral bias associated with these studies, a survey questionnaire was used to determine the relationship between psychiatric disorders and gastrointestinal symptoms. The authors analyzed questionnaires returned by 62,651 persons (66.5% response rate). It was found that the prevalence of anxiety disorder and depression were 15.3% and 10.4%, respectively. The authors’ analysis revealed that anxiety was more strongly associated than depression with gastrointestinal complaints (constipation, diarrhea, and heartburn), but the association was significant in both groups, and that demographic factors, lifestyle factors, and extragastrointestinal complaints could not explain the effect of anxiety disorders and depression on these gastrointestinal symptoms. No conclusion could be made about causality, whether anxiety or depression results from worry about constipation, or whether this symptom can be an expression of the anxiety or depression disorder.

Psychological

A study by Nehra et al demonstrated the prevalence of psychological impairment in patients with rectal evacuation disorders. In the 60 patients included in the study (55 women), psychological disorders were identified in 39 (65%). These disorders were subdivided into the following categories: eating disorders in five, rumination syndrome in three, pain disorder in six, and anxiety-depression in 10, a combination of depression and pain disorder in three, and a combination of eating disorder with anxiety-depression and pain disorder in 12. Since these patients were evaluated as they were undergoing pelvic floor retraining, the association between the psychological status of the patient and the outcome of the retraining was also analyzed. The authors demonstrated that the prevalence of psychological impairment among patients seen for constipation in a tertiary care practice is significant and has a negative impact on the outcome of behavioral treatment.

Eating disorders affect an estimated 5 million Americans every year, and they typically occur in adolescent girls or young women. These illnesses, which include anorexia nervosa, bulimia nervosa, binge-eating disorder, and their variants, are characterized by disturbances in eating, either with restriction of intake or bingeing, as well as excessive concern and distress about body shape and weight. Among the abnormalities associated with eating disorders, somatic indications include diarrhea or constipation, that may be a result of inadequate dietary intake or related to the purging behavior that may be induced by laxatives, enemas, diuretics, anorexic drugs, caffeine, or other stimulants.

Physiological Factors

Metabolic

Measurement of serum electrolytes is an important diagnostic modality in evaluating patients who present with constipation. It is known that electrolyte abnormalities such as hypokalemia, hypo- and hypercalcemia, and metabolic derangements seen in uremia are associated with symptoms of constipation.

Endocrine Disorders

Endocrine disorders are associated with gastrointestinal complications, for example, constipation. Among the endocrinopathies discussed here are diabetes mellitus, hypothyroidism and hyperparathyroidism, multiple endocrine neoplasia type lib (MEN lib), and pregnancy.

The prevalence of gastrointestinal symptoms in individuals with diabetes mellitus is higher as compared to the general population. The impact of diabetes mellitus on gastrointestinal function and quality of life was assessed by Talley et al in a total of 1101 Australian diabetics. Among the gastrointestinal symptoms that were assessed, 24.5% of patients reported having constipation, which was the most prevalent symptom reported among all diabetics, both types 1 and 2. The authors concluded that gastrointestinal morbidity among diabetics is high and is associated with a significant impairment of quality of life. This finding was echoed in another study that concluded that diabetic autonomic neuropathy is a serious and common complication of diabetes, and constipation is the most common lower gastrointestinal symptom. Gastrointestinal function of individuals who have diabetes mellitus and constipation were assessed by scintigraphic colonic transit studies, anal sphincter vector manometry, balloon expulsion defecatory dynamics, and scintigraphic measurement of anorectal angles. Among diabetics with constipation, the study concluded that, compared with community controls, diabetics have a higher prevalence of abnormal evacuation and colonic motor abnormality as manifested by prolonged colonic transit.

The prevalence of bowel dysfunction in hypothyroidism was assessed by a colon transit study among patients who manifested with clinical hypothyroidism. The authors found a significant delay in the whole-gut transit in this population. The authors concluded that hypothyroidism may clinically manifest as a decrease in bowel movements, and is improved by replacement with thyroid hormones. Constipation is a common symptom of hypercalcemia, secondary to hyperparathyroidism.

Delayed orocecal transit studies were reported in pregnancy. There is an increased incidence of constipation and symptomatic hemorrhoids, especially during the latter phases of pregnancy, either as a result of alterations in hormones or secondary to mechanical compression caused by an enlarging uterus.

It is known that the syndrome of MEN lib comprises mucosal ganglioneuromatosis, medullary thyroid carcinoma, pheochromocytoma, and skeletal anomalies. In patients who were found to have ganglioneuromatosis of the alimentary tract, constipation was described as a clinical manifestation of the disorder; megacolon occurred in five of a series of 16 patients.

Other less common endocrinopathies that have been associated with constipation include hyperparathyroidism, panhypopituitarism, pheochromocytoma, and glucagonoma.

Drugs

Table: Constipating medications

Medication class Common medications
Analgesics Opiates, nonsteroidal antiinflammatory drugs
Anticholinergic medications Antispasmodics, antidepressants, and antiparkinsonism drugs
Antacids Aluminum hydroxide and calcium carbonate
Antihypertensives α-adrenergic agonists, beta-blockers, calcium channel blocker,and diuretics
Others Anticonvulsants, iron, bismuth

The following pharmacotherapeutic agents are associated with constipation: analgesics, which include opiates and to a much lesser extent non-steroidal antiinflammatory drugs; anticholinergic medications that are commonly used as antispasmodics, antidepressants, and antiparkinsonism drugs; antacids that contain the elements aluminum and calcium; α-adrenergic agonists, beta-blockers, calcium channel blockers, and diuretic antihypertensives; and other medications such as anticonvulsants, iron, and bismuth.

Neurologic

Neurohumoral integrity is essential for normal gastrointestinal motility, and this is subdivided into intrinsic and extrinsic components. The intrinsic component involves the enteric nervous system; the extrinsic component involves the vagus nerve and splanchnic nerves to the stomach and upper intestine, and the pelvic nerves that supply the distal intestinal segments. In patients with neurologic diseases, colorectal dysfunction is caused by a combination of lesions of the central or peripheral nervous systems, immobility, altered dietary habits, or use of medications such as opioid analgesics and spasmolytics.

Central Nervous System

A variety of colorectal dysfunction can be attributed to lesions of the central nervous system. Those disorders that are seen most commonly in clinical practice will be discussed, namely cerebrovascular accidents, spinal cord injury, multiple sclerosis, Parkinson’s disease, and spina bifida.

The impact of gastrointestinal (GI) complications after an episode of cerebrovascular accident is determined by the extent of the functional impairment related to the event. Initially after the event of a stroke, fecal incontinence is more frequent (31-40%) and is associated with the severity of the stroke; after 6 months, the frequency of fecal incontinence is reduced to 3% to 9%. The frequent association of constipation with disorders involving neuronal malfunction suggests that disruption of the neural modulation of colonic motility may play an important role in the development of constipation. In a study of 8.8 million Medicare patients in the United States, the closest associations were observed between constipation and neurologic diseases. A prospective study to determine the incidence of constipation was conducted on a population of 152 inpatients at a stroke rehabilitation center. The authors found that constipation occurred in 60% of the patients, and that the incidence of constipation was not related to age or gender but was strongly related to functional status of patients as assessed by the Barthel Index.

The prevalence of individuals with spinal cord injury is estimated to be between 183,000 to 230,000, with approximately an 11,000 annual incidence. The pervasive effect of spinal cord injury on the individual involves many systems and results in a variety of impairments that limit adaptive compensation. The impact of gastrointestinal, specifically neurogenic bowel, dysfunction after spinal cord injury can be particularly life limiting. Neurogenic bowel dysfunction is defined as the life-altering impairment of gastrointestinal and anorectal function resulting from a lesion of the nervous system that can lead to life-threatening complications. These symptoms result from interruption of supraspinal control of the sacral parasympathetic supply to the colon, pelvic floor, and anal sphincters. In addition, paralysis and sensory deficits of the limbs can limit independence in the adaptive habits required to compensate for a neurogenic bowel.

Among the plethora of complications associated with neurogenic bowel dysfunction, constipation and difficulty with evacuation have the strongest negative impact on the quality of life of the individual, as it affects as many as 80% of people with spinal cord injury One of the main impediments in the management of neurogenic bowel dysfunction is that common therapeutic modalities used in addressing constipation, such as fiber therapy, do not lead to optimal results and may even exacerbate colonic impairment. Studies assessing the colonic transit in individuals after spinal cord injury, both with the use of colonic markers and colonic scintigraphic studies, have demonstrated that there is a significant delay in individuals with this injury as compared to healthy control groups. In both of these studies, it has been suggested that the significant delay occurs in the rectosigmoid and the descending colon, whereas the transverse, ascending colon, and cecum did not show any significant delays. The authors have suggested that this finding is likely due to the damage to the reflex arches between the colorectum and the sacral spinal cord, thus significantly reducing emptying of the rectosigmoid and descending colon during defecation.

Through the use of solid-state manometric catheters, Fajardo et al evaluated the colonic motor function of the colon of individuals with spinal cord injury and healthy controls. Ambulatory monitoring was made technically possible by attaching the manometric sensors on the colon through the use of endoclips. Prolonged colonic manometric recordings, that is, >24 hours, were made distal to the splenic flexure. The authors concluded that resting colonic motor activity, defined by the motility index, is significantly affected after spinal cord injury when compared to healthy subjects (8.3 ± 3.2 vs. 2.6 ± 0.6, p <.01).

It has been suggested in the literature that colonic motor dysfunction after spinal cord injury is impaired partly due to reduced postprandial colonic motor activity in these individuals. However, it has been demonstrated that although significantly reduced as compared to healthy subjects, there is a significant increase in the motility index of those individuals with spinal cord injury after meal ingestion (2.6 ± 0.6 vs. 4.6 ± 0.7, p < .01). The interesting finding in this study is that there appears to be regional variation in the postprandial response of the colon. The increase in colonic motor activity after meals was seen only in the proximal descending colon (2.8 ± 0.8 vs. 5.8 ± 0.9, p < .03) and not in the distal descending colon (2.5 ± 0.8 vs. 3.2 ± 1.0, p = ns), or rectosigmoid. These observations may help reconcile previous findings including a significant delay of colonic transit in the rectosigmoid area and lack of postprandial increase in colonic motor activity, by demonstrating the importance of the location of the recording system with respect to the likelihood of detecting a gastrocolic response after spinal cord injury. The authors concluded that prolonged transit time in persons with spinal cord injury may be explained by decreased colonic activity, colonic contractions, and intra-luminal pressure. These findings may help to explain the difficulty with bowel evacuation after spinal cord injury, and relief from neurogenic bowel dysfunction should be directed toward modalities that increase colonic motility in general.

The imbalance between the sympathetic-parasympathetic systems resulting from spinal cord injury may lead to disturbances in normal colonic motility, but the specific pathophysiologic mechanism has not yet been defined. The enteric nervous system and the autonomic nervous system, in general, modulate colonic function. Parasympathetic stimulation results in increased colonic contractility, motility, and tone. Thus, it may be inferred that agents or devices that enhance parasympathetic tone (such as neuroprosthetic stimulation of the sacral nerves or pharmacologic interventions) may be important adjuncts in the management of neurogenic bowel dysfunction.

The incidence and prevalence of multiple sclerosis in the United States are estimated to be 3.2 per 100,000 persons and 58.3 per 100,000 persons, respectively The prevalence of gastrointestinal complaints in individuals afflicted with multiple sclerosis is high and is associated with neurogenic dysfunction of other organ systems. Bowel symptoms are common; at least 52% of patients in one series had constipation, fecal incontinence, or both, while other studies have shown that the prevalence of constipation varies from 2% to 20%. As in individuals with spinal cord injury, neurogenic bowel dysfunction secondary to multiple sclerosis is a source of considerable psychosocial impairment. Indeed, among individuals with multiple sclerosis, bladder and bowel symptoms were rated as the third most important factors, after spasticity and incoordination, associated with the limitations on their ability to work.

Colonic transit time in individuals with multiple sclerosis was assessed by means of radiopaque markers and was found to be significantly delayed, suggesting either a disturbance in decreased colonic motor activity or outlet dysfunction. Colonic compliance was found to be reduced in individuals with multiple sclerosis as colonometrograms demonstrated a more rapid pressure rise in the multiple sclerosis group than in the control group; likewise, the multiple sclerosis group failed to demonstrate the postprandial increase in colonic motor and myoelectrical activity that was observed in the control group. The authors suggested that these findings may be features of visceral neuropathy in patients with multiple sclerosis and severe constipation.

Pelvic floor dysfunction has been demonstrated in individuals who have constipation and multiple sclerosis. Anorectal physiology testing of individuals with multiple sclerosis and constipation revealed that paradoxical puborectalis contraction is common among these individuals, and it was proposed that such is a feature of the disturbed voluntary sphincter control mechanism, analogous to detrusor sphincter dyssynergia in the bladder. In addition to the physiologic abnormalities of the gastrointestinal tract that are reputed to be associated with multiple sclerosis, medications such as anticholinergics and muscle relaxants are possible contributors to constipation. Bowel management in multiple sclerosis is challenging and is currently empirical, mainly because the underlying illness is progressively debilitating and is not reversible. Treatment of constipation is important, as a distended rectum may worsen bladder symptoms, and constipation may lead to increased limb spasticity Empiric recommendations are the starting point of therapy, which include maintaining a high-fiber diet, high fluid intake, and physical exercise.

Gastrointestinal impairment, specifically constipation, in individuals with Parkinson’s disease is common and prevalent, occurring in as many as two thirds of the patients diagnosed with the disease. In a study by Siddiqui et al involving 68 patients diagnosed with Parkinson’s disease, autonomic dysfunction was assessed by comparing gastrointestinal, urinary, sexual, cardiovascular, and thermoregulatory symptoms with a matched control group. The study found that patient’s with Parkinson’s disease experienced a higher frequency and severity of autonomic dysfunction, and that among the gastrointestinal symptoms that were assessed, patients reported decreased bowel movements as compared to controls (20.4% vs. 0%, p < .02).

The cause of the disturbances in gastrointestinal function after Parkinson’s disease is uncertain. The effect of antiparkinsonian medication as a possible etiology for gastrointestinal dysfunction in Parkinson’s disease is largely overestimated, although it certainly has an influence and should be adapted accordingly in patients with GI motility disorders; in particular, anti-cholinergic drugs should be avoided. Recent evidence suggests that the gastrointestinal symptoms seen in Parkinson’s disease are related to the Parkinson’s disease process itself rather than to the medications. The effects of the disease on skeletal muscles parallel the severity and duration of the dysfunction seen in the oropharynx, anorectum, and pelvic floor, and are thus implicated as possible etiologic factors for the morbidity Evidence suggests that neuropathologic abnormalities in the enteric nervous system analogous to those anomalies regarded as pathognomonic of the parkinsonian process in the central nervous system demonstrate parallel pathologic changes in a number of disease processes previously regarded as confined to the central and somatic nervous systems. Depletion of dopamine-containing neurons in the central nervous system is a basic defect in Parkinson’s disease.

Immunohistochemistry staining of myenteric and submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal polypeptide (VIP) in Parkinson’s disease patients revealed that the number of dopaminergic myenteric neurons is significantly decreased. When compared with controls, patients with Parkinson’s disease had a mean (in percentage) of 0.4 ± 0.2 vs. 6.9 ± 2.3 in controls. The authors have suggested that the identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinson’s disease may offer a plausible explanation for the disturbances in gastrointestinal function in these individuals.

Patients with tethered cord syndrome, whether secondary to myelodysplasia, presacral mass, or sacral hemivertebrae, were found to have a higher prevalence of constipation and fecal and urinary incontinence. Untethering of the cord was performed in 18 patients, and none noted improvement in their bowel symptoms.

Peripheral Nervous System

Gastrointestinal dysfunction, specifically slow-transit constipation, generally is a moderate to severe disorder, and more often than not is of unknown etiology. The involvement of the peripheral nervous system (somatic-sensory and autonomic nervous system) is implicated as a conceivable etiology of this dysfunction.

Among the disorders of the peripheral nervous system that will be discussed are familial autonomic neuropathy, neurofibromatosis, and paraneoplastic and antineuronal visceral neuropathy.

Autonomic neuropathy can be familial in nature. In a cohort of patients who have slow-transit constipation of unknown etiology, quantitative sensory and autonomic tests revealed that there is evidence of small fiber neuropathy. There is also a high incidence of a positive family history, particularly a possible association with Hirschsprung’s disease. The authors suggest investigation for possible genetic basis, and the exact mechanism of the disease remains unknown.

Neurofibromatosis is a group of autosomal dominant diseases that occur in three principal forms: (1) hyperplasia of the submucosal and myenteric nerve plexuses and mucosal ganglioneuromatosis, which leads to disordered gut motility (discussed in the endocrine disorders); (2) gastrointestinal stromal tumors showing varying degrees of neural or smooth muscle differentiation; and (3) a distinctive glandular, somatostatinrich carcinoid of the periampullary region of the duodenum that contains psammoma bodies. Neurofibromatosis has been described as diffusely involving the entire gastrointestinal tract, which can lead to a disorder in gut motility manifesting as constipation, luminal obstruction, or intussusception.

It has been reported that antineuronal antibodies were found in some patients with severe gut dysmotility of unknown etiology Postmortem analysis of the gastrointestinal tracts of individuals who had paraneoplastic visceral neuropathy is characterized by neuronal and axonal degeneration, lymphoplastic infiltration, and glial cell proliferation within the myenteric plexus. Often, these patients manifested with severe gastrointestinal dysfunction that included constipation, obstipation, and intestinal pseudo-obstruction.

Connective Tissue Diseases

Connective tissue diseases are associated with a wide spectrum of disorders involving the gastrointestinal system. In a study by Trezza et al, the impact of systemic sclerosis on bowel function was assessed by determining the frequency and severity of colorectal problems among patients with systemic sclerosis. Among 83 respondents (86%), 16% did not have a normal desire to defecate and 18% regularly needed digital stimulation or evacuation of the rectum. Among these respondents who complained of significant impairment associated with their systemic sclerosis, 20% reported that colorectal dysfunction caused some or a major restriction of social activities or their quality of life. The authors concluded that colorectal dysfunction is very common among patients with systemic sclerosis, and that this problem often leads to restriction of their social activities and significant impairment in their quality of life.

In a study that assessed gastrointestinal transit through the esophagus, stomach, and small and large intestine of patients with progressive systemic sclerosis, Wegener et al noted differences in patients and controls. Using radiopaque markers, the authors found that in the subset of patients who complained of constipation, two of three had a whole-gut transit time outside the range of the control group, suggesting that in this disorder the complaint of constipation is associated with colonic motor dysfunction. In 1998 Weston et al characterized gastrointestinal disturbances seen in a tertiary care referral center. A total of 62 patients, 45 of whom were women, with scleroderma (46 patients), mixed-connective tissue disease (eight patients), and polymyositis or dermatomyositis (eight patients) were included in the study. Among the gastrointestinal symptoms that were seen at the time of the patients’ presentation, constipation was observed in 31% of the cohort. The authors likewise observed that there was a higher prevalence of constipation in those with more than 5 years of the diagnosis, and that there was a higher prevalence of pseudo-obstruction and small bowel dilatation or diverticulosis in patients with less than 5 years of the diagnosis.

Infiltrative Diseases

Infiltrative diseases, for example amyloidosis, of the colon as the etiology of constipation are typically rare. Amyloidosis refers to a group of disorders characterized by the extracellular accumulation of insoluble, fibrillar proteins (amyloid). In a case report in an elderly patient who presented with intestinal pseudo-obstruction and had a subsequent colectomy, immunohistochemical analysis of the resected transverse colon revealed massive deposits of amyloid proteins composed of lambda light chains in the interstitial, connective, perivascular tissue and muscula tunica, suggestive of a diagnosis of amyloidosis. Common clinical features of amyloidosis include gastrointestinal disorders that often manifest as constipation. In a cohort of women who were diagnosed with amyloidosis by detection of amyloid in subcutaneous fat tissue, 63% of these patients were found to have constipation, compared with 25% in the matched control group. In the same study, it was found that the prevalence of constipation was more common than the presence of proteinuria or renal insufficiency In a study that compared the clinical symptoms, specifically gastrointestinal disturbances of Swedish and Japanese patients with familial amyloidotic polyneuropathy, the authors reported that the initial gastrointestinal symptom in the majority of the Japanese patients is diarrhea, whereas in the Swedish patients the initial symptoms are commonly nausea, vomiting, and constipation. However, at the final stages of the disease, patients are usually incapacitated, suffering from pronounced malabsorption, and death is usually caused by extreme malnutrition and infections.

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